Good news! Defeating one virus at a time! The use of nanoparticles to isolate the glycoproteins of a virus could be a breakthrough applicable to other viruses as well!
This time it will help people living mostly in West Africa!
"... Now, scientists ... have determined the structure of the critical protein complex that lets Lassa virus infect human cells. ...
Like many viruses, Lassa virus exists in a variety of lineages, each with slight variations in its genes. This diversity has made it challenging to pinpoint antibodies that recognize all versions of Lassa virus. Scientists have also struggled to isolate Lassa glycoproteins—the spike-like proteins that surround the virus and are the target of most antibodies. In the infectious virus, these glycoproteins exist in complexes of three, called trimers. For decades, however, scientists were only able to isolate glycoproteins in the lab as single proteins and not in their trimer complexes.
In 2022, ... discovered how to use nanoparticles to hold the glycoproteins together into trimers. In the new work, they used that technique to isolate and structurally characterize trimers of the glycoproteins from four different Lassa virus lineages. Surprisingly, the glycoprotein structures from the distinct lineages were extremely similar. ..."
From the highlights and abstract:
"Highlights
• Stabilization of diverse Lassa virus glycoproteins enables their structural characterization
• mAb 12.1F, belonging to the GP1-A cluster, inhibits matriglycan and LAMP-1 binding
• GP1-A mAbs show glycan dependence with 19.7E demonstrating lineage-dependent binding
• A trimer-preferring Ab S370.7 targets the GPC-B epitope
Summary
Lassa fever is an acute hemorrhagic fever caused by the zoonotic Lassa virus (LASV). The LASV glycoprotein complex (GPC) mediates viral entry and is the sole target for neutralizing antibodies. Immunogen design is complicated by the metastable nature of recombinant GPCs and the antigenic differences among phylogenetically distinct LASV lineages. Despite the sequence diversity of the GPC, structures of most lineages are lacking. We present the development and characterization of prefusion-stabilized, trimeric GPCs of LASV lineages II, V, and VII, revealing structural conservation despite sequence diversity. High-resolution structures and biophysical characterization of the GPC in complex with GP1-A-specific antibodies suggest their neutralization mechanisms. Finally, we present the isolation and characterization of a trimer-preferring neutralizing antibody belonging to the GPC-B competition group with an epitope that spans adjacent protomers and includes the fusion peptide. Our work provides molecular detail information on LASV antigenic diversity and will guide efforts to design pan-LASV vaccines."
Structural conservation of Lassa virus glycoproteins and recognition by neutralizing antibodies (open access)
Graphical abstract
Figure 2Site-specific glycosylation and structural analysis of LASV GPCs from different lineages
No comments:
Post a Comment